No abstract

High-risk human papillomavirus (HPV) DNA detection provides high sensitivity but low specificity for moderate-grade cervical intraepithelial neoplasia or worse histological identification. A prospective study evaluated mRNA testing efficacy for predicting this histological diagnosis in case of HPV 16 and/or 18 DNA detection. A total of 165 endocervical samples harboring HPV 16 and/or 18 DNA were tested with NucliSENS-EasyQ® HPV E6/E7-mRNA-assay (Biomerieux, Marcy l´Etoile, France). Women with cytological alterations were referred to colposcopy (n = 111). Moderate-grade cervical intraepithelial neoplasia or worse was diagnosed in 25.8% of women presenting atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions and in 89.8% of women with high-grade squamous intraepithelial lesions. mRNA sensitivity was 81.3% and 84.1%, respectively. Specificity was 52.2%, and 80.0%, respectively. Negative predictive value (NPV) was 88.9% in undetermined or low-grade squamous lesions. Positive predictive value (PPV) was 97.4% in high-grade squamous lesions. mRNA reduced colposcopies by 44.3% in undetermined or low-grade squamous lesions. Direct treatment of mRNA-positive cases reduced 77.5% of colposcopies in high-grade squamous lesions. Women without cytological alterations were followed for 18 months (n = 35), and moderate-grade cervical intraepithelial neoplasia or worse was diagnosed in 34.3%; mRNA sensitivity and specificity were 83.3% and 86.9%, respectively. PPV and NPV were 76.9% and 90.9%, respectively for predicting moderate-grade cervical intraepithelial neoplasia or worse in 18 months. mRNA reduced the number of visits for follow-up in 62.2%. In conclusion, NucliSENS-EasyQ® HPV E6/E7-mRNA-assay (Biomerieux) can serve as a triage test in case of HPV 16 and/or 18 DNA detection.

assistance in obtaining the SEM images and specimen preparation respectively. Contributors listMatthew Martin carried out this study as part of his intercalated BSc project and took part in all aspects of the research. Emma Chung was responsible for routine supervision, study design and writing the paper. Alison Goodall supervised the preparation of thrombus samples. Alberto Della Martina created the microbubbles. Kumar Ramnarine supervised the flow-rig measurements. Lingke Fan wrote the software used for data collection and analysis.Sarah Hainsworth obtained the SEM images. A. Ross Naylor and David H. Evans were responsible for overall supervision. All authors have read and approved the final manuscript. Enhanced detection of thrombo-emboli using targeted microbubblesCover title: Microbubble enhanced thrombo-embolus detection Word count: 4051 words Abstract (222 words) Background and Purpose: Targeted ultrasound contrast agents have recently been developed to adhere selectively to specific pathogenic materials such as plaque or thrombus. Administration of such microbubbles has potential to aid transcranial Doppler ultrasound (TCD) detection of emboli, and to act as markers for distinguishing one embolic material from another. The purpose of this study was to investigate whether TCD detection of circulating thrombus emboli would be enhanced by the addition of targeted microbubbles. Methods: Binding of microbubbles to the surface of the thrombus was confirmed using Scanning Electron Microscopy. Targeted and control bubbles were then introduced to thrombus and tissue-mimicking material circulated under pulsatile flow conditions in an in vitro flow-rig. Embolic signal intensities before and after introduction of the bubbles were measured using transcranial Doppler ultrasound. Results: Targeted microbubbles enhanced Doppler signal intensities from thrombus emboli by up to 13 dB. The bubbles were capable of binding to moving thrombus when injected into the flow-circuit in low concentrations (~ 30 bubbles per 100 ml), and were retained on the thrombus under pulsatile-flow conditions. Signal intensities from similarly sized pieces of tissue mimicking material were not enhanced by injection of targeted bubbles.Conclusions: Injection of appropriately targeted microbubbles significantly enhances ultrasound detection of circulating thrombus emboli in vitro, and has potential to assist clinicians in distinguishing thrombus emboli from atheromatous plaque.

No abstract

No abstract